The dendritic cells principally are kind of special antigen-presenting cells performing the function of presenting antigen to a T cell, and present in a type of a spatial dendrite in a lymphatic gland, a spleen, the thymus, under the skin, or the intercellular spaces of various tissues. The dendritic cells play an important role in activating T cells by presenting various antigen samples along with MHC (major histocompatibility complex) Class I or MHC Class II complex to a T cell by absorbing an antigen in cells.
The dendritic cells are differentiated in a state of different maturities according to a type of environmental signal present around the cells, and thus, exist as immature, semi-mature, or mature dendritic cells. The immature dendritic cells are discovered at an initial maturity state and perform a primary function collecting and removing debris from transcellular fluid. However, the immature dendritic cells express the inflammatory cytokine in the low level, and thus, even when the cells contact with a T cell, the cells cannot activate a T cell. On the other hand, the mature dendritic cells allow a naive T cell to be activated, and thus, have ability capable of inducing an immune reaction. In order for the immature dendritic cells to be differentiated into the mature dendritic cells, the immature dendritic cells should be exposed to many specific signals to activate a toll-like acceptor. For this reason, many co-stimulatory molecules and proinflammatory cytokine like IL-12 are up-regulated and transferred from tissues to a lymphatic gland, and thus, the projections like fingers, which are the morphological feature of the mature dendritic cells, are appeared.
Meanwhile, in the case where the immature dendritic cells are in different environmental conditions, they may be differentiated into the semi-mature dendritic cells. For example, it may be considered that TNF-α (tumor necrosis factor-α) that releases from the cells during an apoptosis process contributes the differentiation into the semi-mature dendritic cells. The semi-mature dendritic cells become exhibit some of the characteristics of phenotype of the mature dendritic cells after losing some of the characteristics of the immature dendritic cells.
Recently, a study on a therapy for treating cancers or immune-related diseases using the dendritic cells is being performed. For example, Korean Patent Laid-Open Publication No. 10-2010-0109099 discloses the mature dendritic cells for treating a cancer, in which the mature dendritic cells are matured by sensitizing the immature dendritic cells with a cancer-specific antigen protein and Korean Patent No. 10-0524817 discloses the dendritic cells for treating type I diabetes and rheumatoid arthritis, in which the dendritic cells are prepared by treating the immature lymphatic dendritic cells with interferon-gamma. In addition, M. B. Lutz, et al. (J. Exp. Med, 2002, 195(1): 15-21) suggest the experimental results, in which the dendritic cells treated with TNF-α can suppress encephalomyelitis in a C57BL/6 mouse. However, up to now, there are no developments of the tolerogenic dendritic cells having the therapy effect for treating a myocardial infarction.
Therefore, the present inventors studied for developing the tolerogenic dendritic cells for treating cardiac insufficiency that occurs by excessive remodeling of left ventricle in the heart muscle recovery process after an acute myocardial infarction, in which there are no proper therapies for treating the cardiac insufficiency, and as a result, the inventors found that the remodeling of left ventricle is inhibited and the inflammation is alleviated when the tolerogenic dendritic cells are treated to the mouse model with an acute myocardial infarction. Thus, the inventors finally completed the present invention.